Background Asia is experiencing a rapid rise in the incidence of type 2 diabetes mellitus (T2DM), characterised by impaired glucose tolerance and insulin resistance. Environmental variables such as dietary habits, physical inactivity, and urbanisation, as well as genetic vulnerability, contribute to the development of T2DM. Mutations in the TCF7L2 gene, particularly rs7903146, have been extensively researched for their potential significance in disease development and metabolic abnormalities, including dyslipidaemia leading to cardiovascular disease. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 principles. We reviewed six electronic databases—PubMed, Google Scholar, ResearchGate, Scopus, ScienceDirect and Web of Science—for studies published before 21 January 2024. Eligible studies comprised cross-sectional, case–control, cohort and meta-analysis that investigated the link between the TCF7L2 rs7903146 variation and T2DM, as well as its relationship to biomarkers. Results A total of 22 articles were included. Among these, 17 studies showed a significant association of the rs7903146 polymorphism in the TCF7L2 gene with T2DM, while 5 studies did not. Based on 14 eligible studies of Asian populations, a forest plot was established, most of the studies showing ORs greater than 1.0 and association with T2DM. The significant result was discovered in a Chinese study (OR=1.98, 95% CI: 1.13 to 3.49), and the pooled trend was suggestive for a higher risk of T2DM for the T allele carriers. Effect size estimates were heterogeneous, and some margins of East Asian genetic variants were non-significant. Furthermore, TCF7L2 variants have been associated with a variety of biomedical markers, including lipid profiles, glucose, triglycerides and total cholesterol; however, the results from different investigations are conflicting. Conclusions The TCF7L2 rs7903146 variation has been systematically linked to an increased risk of T2DM, indicating its potential as a genetic risk marker. However, the diversity in its relationship with biomarkers implies that additional factors, such as gene–environment interactions and population-specific genetic backgrounds, play important roles in disease development. A comprehensive understanding of this variation may benefit in T2DM prevention and individualised treatment approaches.
Sen et al. (Mon,) studied this question.
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